From single agent trials to combination: focused development programs to improve immunotherapy of solid tumors.

CC-1 is a PSMA×CD3 TCE in an IgG-based format, being evaluated in trials enrolling patients with advanced as well as biochemically recurrent prostate cancer.

• Modality: S1: PSMA × CD3 TCE
• Stage: Phase I · dose expansion
• Indication: Prostate cancer

Role in the platform. As a Signal 1 agent, CC-1 supplies the ignition: tumor-directed T cell activation that can be boosted by a TWYCE BiCo.

• Founding publication — EMBO Molecular Medicine (2020)
• Phase I trial in castration-resistant prostate cancer — NCT04104607
• Trial in biochemically recurrent prostate cancer — NCT05646550

CC-2 is an FLT3 × CD3 bispecific antibody from our TCE program, licensed to Cullinan and currently in Phase 2 clinical development in AML.

• Modality: S1: FLT3 × CD3 TCE
• Stage: Phase II clinical development (Cullinan)
• Focus: AML

CC-3 is a B7-H3 (CD276)×CD3 TCE in an IgG-based format, being evaluated in a Phase I basket study.

• Modality: S1: B7-H3 × CD3 TCE
• Stage: Phase I · dose escalation
• Focus: solid tumors · clinical trial enrolling colorectal cancer, breast cancer, penile cancer, sarcoma

Role in the platform. As a Signal 1 agent, CC-3 supplies the ignition: tumor-directed T cell activation that can be boosted by a TWYCE BiCo.

• Founding publication — Molecular Therapy (2023)
• Phase I trial — NCT05999396

BiCo-3 is our lead Signal 2 candidate: a FAP×CD28 bispecific designed to deliver fully target-restricted CD28 costimulation anchored in the TME.

• Modality: S2: FAP × CD28 bispecific costimulator
• Stage: Preclinical PoC complete · IND filing of first-in-human study
• Focus: solid tumors · clinical trial planning to enroll colorectal cancer, breast cancer, penile cancer, sarcoma

FAP is specific to tumor stroma, allowing costimulation to be delivered where T cell activity is often suppressed.

• Founding publication — bioRxiv preprint (2026), JCI in press

The combination of BiCo-3 with our own Signal 1 clinical programs — CC-1 and CC-3 — combines tumor-directed T cell activation and TME-anchored costimulation.

• Modality: S1: CC-1 (PSMA × CD3) or CC-3 (B7-H3 × CD3) · S2: BiCo-3 (FAP × CD28)
• Stage: Planned combination arm of the first-in-human trial
• Focus: solid tumors · basket trial

Two functionally interdependent molecules, directed to two different targets with non-overlapping expression in healthy tissues, allow for increased tumor specificity and thus reduced side effects. Providing Signal 1 and Signal 2 induces superior and sustained T cell antitumor reactivity.

Built on clinically validated TCEs. Both candidate Signal 1 compounds are already being evaluated in Phase I trials, allowing for rapid development of the combination.

Development stage. Planned as a combination arm after dose escalation of BiCo-3 in the FIH trial: CC-1 or CC-3 provide Signal 1, BiCo-3 supplies Signal 2.

• Founding publication — bioRxiv preprint (2026), JCI in press

Pairing BiCo-3 with a peptide vaccine replaces the antibody-delivered Signal 1 with vaccine-induced T cell priming, while the CD28 signal is still provided at the TME.

• Modality: S1: Peptide vaccine (HLA-presented antigens) · S2: BiCo-3 (FAP × CD28)
• Stage: Planned combination arm of the first-in-human trial
• Focus: solid tumors · basket trial

A different first signal. Where a CD3 engager redirects T cells, vaccination primes them — the costimulatory component of the platform remains the same.

Why combine. Cancer vaccines create tumor-specific T cells, but their antitumor reactivity is impaired by the suppressive TME. BiCo-3 provides TME-anchored costimulation.

Why a peptide vaccine. Defined peptide antigens offer off-the-shelf potential and access to intracellular antigens via HLA presentation, and the program builds on Tübingen’s long-standing strength in peptide and T cell immunology.

Development stage. Planned as a combination arm of the BiCo-3 first-in-human study.

Smart TriCo is a TAA × CD3 × CD28 trispecific antibody: both signals in one molecule, with activation restricted to the tumor.

• Modality: S1 + S2: TAA × CD3 × CD28 trispecific Ab
• Stage: Preclinical
• Focus: Selected tumor setting

Development stage. Smart TriCo is in preclinical development.